Testing the Safety of Anti-Cancer Drug, CX-5461 (Pidnarulex), in Treating Lymphoma With Specific Changes in the MYC Gene

NCT ID: NCT07069699

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-03-31

Study Completion Date

2027-09-19

Brief Summary

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This phase Ib/II trial tests the safety, side effects, best dose and how well giving CX-5461 works for the treatment of patients with B-cell non-Hodgkin lymphoma. CX-5461 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CX-5461 may be safe, tolerable and/or effective in treating patients with B-cell non-Hodgkin lymphoma.

Detailed Description

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PRIMARY OBJECTIVES:

I. To define dose limiting toxicity (DLT). II. To assess toxicity profile. III. To determine the recommended phase 2 dose (RP2D). IV. To determine the objective response rate (ORR) (complete response \[CR\] and partial response \[PR\]).

V. To perform pharmacokinetic (PK) studies. VI. To examine the effect of CX-5461 (Pidnarulex) on gene expression profile of MYC aberrant lymphomas.

SECONDARY OBJECTIVE:

I. To observe and record anti-tumor activity.

EXPLORATORY OBJECTIVES:

I. To determine the mechanisms of response and resistance using circulating tumor deoxyribonucleic acid (ctDNA).

II. To observe cerebral spinal fluid (CSF) distribution of CX-5461 (Pidnarulex).

OUTLINE: This is a dose-escalation study of CX-5461 followed by a dose-expansion study.

Patients receive CX-5461 intravenously (IV) over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture with cerebrospinal fluid (CSF) collection on study and positron emission tomography (PET) scan/computed tomography (CT) scan, tumor biopsy, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up every 3-4 months for 2 years then every 6 months for years 3-5.

Conditions

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Burkitt Lymphoma Double-Expressor Lymphoma High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (CX-5461)

Patients receive CX-5461 IV over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture with CSF collection on study and PET scan/CT scan, tumor biopsy, and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo tumor biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo CSF and blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo PET/CT scan

Lumbar Puncture

Intervention Type PROCEDURE

Undergo lumbar puncture

Pidnarulex

Intervention Type DRUG

Given IV

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT scan

Interventions

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Biopsy Procedure

Undergo tumor biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo CSF and blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo PET/CT scan

Intervention Type PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

Intervention Type PROCEDURE

Pidnarulex

Given IV

Intervention Type DRUG

Positron Emission Tomography

Undergo PET/CT scan

Intervention Type PROCEDURE

Other Intervention Names

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Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography LP Spinal Tap CX-5461 CX5461 Pol I Inhibitor CX5461 RNA Pol I Inhibitor CX5461 Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT

Eligibility Criteria

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Inclusion Criteria

* Patients must have one of the following subtypes of aggressive B-cell non-Hodgkin lymphomas: double-expressor lymphoma (DEL), high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangement, or Burkitt lymphoma (BL). Eligible patients must have received at least one prior line of treatment and must have disease for which no standard curative or palliative treatment options exist or remain effective
* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of CX-5461 (Pidnarulex) in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%). ECOG 3 is allowed if directly related to lymphoma per treating provider
* Absolute neutrophil count ≥ 1,000/mcL
* Platelets ≥ 50,000/mcL
* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional upper limit of normal (ULN)
* Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Patients with cytopenia related to abnormal bone marrow function in the setting of bone marrow involvement with lymphoma or post chimeric antigen receptor (CAR) T-cell are allowed to enroll if deemed safe by treating provider
* Patients without clinical evidence of central nervous system (CNS) lymphoma
* The effects of CX-5461 (Pidnarulex) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) 14 days prior to study entry and for the duration of study participation and for at least 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking CX-5461 (Pidnarulex) and for 6 months after cessation of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception 14 days prior to the study, for the duration of study participation, and 6 months after completion of CX-5461 (Pidnarulex) administration. Women of childbearing age should not donate egg(s) and men should not donate sperm for the duration of study participation and 6 months after completion of the last dose CX-5461 (Pidnarulex)
* Willingness to provide blood and biopsy samples for research purposes
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

* Patients must have recovered from clinically significant adverse events (AEs) of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia)
* Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of CX-5461 (Pidnarulex) will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. For medications or substances not listed, or in cases of uncertainty, the Principal Investigator may consult with a medical expert or a pharmacologist to make an informed decision regarding eligibility
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CX-5461 (Pidnarulex)
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* Pregnant women are excluded from this study because CX-5461 (Pidnarulex) is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with CX-5461 (Pidnarulex), breastfeeding should be discontinued if the mother is treated with CX-5461 (Pidnarulex)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sami Ibrahimi

Role: PRINCIPAL_INVESTIGATOR

Yale University Cancer Center LAO

Other Identifiers

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NCI-2025-04787

Identifier Type: REGISTRY

Identifier Source: secondary_id

10717

Identifier Type: OTHER

Identifier Source: secondary_id

10717

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA186689

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2025-04787

Identifier Type: -

Identifier Source: org_study_id